Neuromuscular Blocking Agent Anaphylaxis

Neuromuscular blocking agent (NMBA) anaphylaxis is an immediate hypersensitivity reaction to a muscle relaxant, the leading cause of perioperative anaphylaxis.

Epidemiology. NMBAs are the cause in 50% to 60% of confirmed cases, and the risk is highest with succinylcholine and rocuronium (about 1 in 2,500 to 1 in 5,000 exposures), and lower with atracurium and vecuronium. Cross-reactivity between NMBAs occurs in about 60% to 70% of those sensitised.

Risk factors. Female sex, previous exposure to quaternary ammonium compounds (cosmetics, disinfectants, cough syrups, pholcodine historically), and previous NMBA exposure. Many patients react on first exposure.

Pathophysiology.

IgE antibodies bind quaternary or tertiary ammonium epitopes on the drug, causing mast cell degranulation. Non-immune histamine release (atracurium, mivacurium, tubocurarine) causes milder reactions through MRGPRX2 receptor activation.

Onset 1 to 10 minutes after injection: hypotension, bronchospasm, tachycardia, flushing, urticaria, angioedema and collapse. The skin may show nothing under drapes.

Red flags.

• Refractory hypotension.
• Bronchospasm with rising airway pressure.
• Loss of capnography trace.

Serial tryptase (1 hour, 3 to 6 hours, baseline). Allergy testing at 4 to 6 weeks: skin prick and intradermal tests with all NMBAs (to identify safe alternatives), specific IgE to quaternary ammonium (morphine, pholcodine), and basophil activation testing. Test at least 4 weeks and not more than 6 months after the reaction.

Differential diagnosis.

• Non-immune histamine release.
• Bronchospasm.
• High spinal block.
• Other anaphylaxis triggers.
• Pulmonary embolism.

Stop the suspected drug and other triggers, call for help, give 100% oxygen, and secure the airway.

• Adrenaline: 50 microgram IV titrated every 1 to 2 minutes, then infusion 0.05 to 0.1 microgram/kg/min; 0.5 mg IM if no IV access; in arrest 1 mg IV every 3 to 5 minutes; monitor ECG and blood pressure; avoid excess in ischaemia; children 1 microgram/kg IV or 10 microgram/kg IM.
• Crystalloid: 20 mL/kg IV rapidly, repeated as needed.
• Noradrenaline: 0.05 to 0.5 microgram/kg/min for refractory hypotension.
• Salbutamol: 5 mg nebulised for bronchospasm.
• Hydrocortisone 200 mg IV once and chlorphenamine 10 mg slow IV as adjuncts; maximum hydrocortisone 400 mg and chlorphenamine 20 mg in 24 hours.
• Sugammadex may bind rocuronium, but its use is contested; where a reversal is needed, give 16 mg/kg IV once, monitoring for hypersensitivity (maximum 16 mg/kg; avoid if creatinine clearance is under 30 mL/min).

Admit to intensive care for at least 12 to 24 hours.

Follow up. Allergy referral, written record of the suspected agent and safe alternatives, patient alert card and national reporting. Avoid all NMBAs until tested, or choose a tested negative agent. Use regional or non-relaxant techniques where feasible.

Monitoring. Haemodynamics, airway pressure, saturation and tryptase.

Referral and escalation. Critical care and allergy service.